Voltage-gated Na and Ca2+ channels represent two major ion channel families that enable
myriad biological functions including the generation of action potentials and the coupling of electrical
and chemical signaling in cells. Calmodulin regulation (calmodulation) of these ion channels comprises
a vital feedback mechanism with distinct physiological implications. Though long-sought, a
shared understanding of the channel families remained elusive for two decades as the functional manifestations
and the structural underpinnings of this modulation often appeared to diverge. Here, we review
recent advancements in the understanding of calmodulation of Ca2+ and Na channels that suggest
a remarkable similarity in their regulatory scheme. This interrelation between the two channel families now paves the way
towards a unified mechanistic framework to understand vital calmodulin-dependent feedback and offers shared principles
to approach related channelopathic diseases. An exciting era of synergistic study now looms.
Keywords: Sodium channels, calcium channels, calmodulation.
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